The rise in dementia cases has led to calls for behavioral interventions to enhance brain health to delay the onset or progression of cognitive impairment. There is growing evidence of the cognitive benefits of exercise, but less is known about combined interventions. Our primary goal is to replicate and extend our recently concluded randomized clinical trial (RCT) investigating interactive physical and mental exercise, Cybercycling for Cognitive Health (Anderson-Hanley et al., 2012a). This RCT was conducted by the PI and collaborators with 63 independent living older adults. We found significant cognitive benefit after three months of simultaneously combined physical and mental exercise (i.e., exergaming), when contrasted with physical exercise alone. We compared physical exercise on a traditional stationary bike, with interactive physical and mental exercise on a cybercycle. A cybercycle is a virtual reality-enhanced stationary bike with interactive cycling tours, on-screen competitors, and videogame capabilities. Results suggest that for the same effort, interactive physical and mental exercise on a cybercycle can yield greater cognitive benefit than physical exercise alone on a stationary bike. We wish to extend our research to persons with mild cognitive impairment (MCI), to examine the generalizability of the above finding to those already experiencing cognitive decline, with the hypothesis that cybercycling can slow decline more than either physical or mental exercise alone. We also aim to add to the scientific understanding of the phenomenon of increased cognitive benefit when physical and cognitive exercises are interactive, by comparing cybercycling with mental and physical exercise implemented individually. The primary method of this study will be an RCT (Aim 1), and we propose to enroll 81 patients with MCI. Participants will be randomized into one of three conditions for six months: cybercycle, stationary bike alone, or videogame alone. Comprehensive evaluations will include: neuropsychological (e.g., executive function and memory), behavioral (e.g., compliance and effort/watts), physiological (e.g., cardiorespiratory fitness), biomarker (e.g., BDNF), [deleted EEG/ERP] and an expanded neuroimaging pilot (n=30 MRI; Anderson-Hanley et al., 2012b). We expect that cognitive benefit will be greatest for the cybercycle condition, followed by physical exercise alone, and finally a smaller effect from mental exercise alone. To clarify mechanisms linking exercise to cognitive change (Aim 2), we will conduct secondary analyses of behavioral, physiological, biomarker, [deleted neurophysiological], and neuroimaging data. We plan to translate our scientific findings for application in the public health sphere, by synthesizing our results in presentations and publications, which should lead to wide dissemination and implications for interventions for persons with MCI (e.g., cybercycle placement in assisted living or home environments; Aim 3).